Patent GB-1390951-A (GB)
Title: 18-amino-and acylamino-14beta,16beta,20-trihydroxysteroids and their manufacture
IPC: C07J71/00
Filed: 1972-03-20
Abstract: 1390951 18 - Acylamino- and 18 - amino- 14,16,20 - trihydroxy - steroids SCHERING AG 20 March 1972 [23 March 1971 14 Jan 1972 27 Jan 1972] 12807/72 Heading C2U Novel steroids of the formulae   wherein each R is H or acyl of up to 5 carbon atoms; each R<SP>1</SP> is acyl of up to 5 carbon atoms; R 1  is H or C 1-6  alkyl; X is halogen or free or esterified OH; Y is H, acyl or alkyl; and Z is O, H 2  or H(OR 2 ) in which R 2  is H or acyl and OR 2  is in the α- or #-configuration are prepared from starting materials of the Formula (I) via intermediates of the other formulae given below wherein Y<SP>1</SP> is acyl or alkyl, and T is triarylmethyl. Thus (I) is reduced to a corresponding 20-ol, this is treated with lead tetraacetate in the presence of iodine to give (II), this is hydrolysed to (IIa), this, after acylation of any free 3-OH group is oxidized to (III), this is either (i) treated with chromium-(II)-acetate in the presence of an organic base to give (IV) and this reduced with a lithium-aluminium trialkoxyhydride to give (V) or, preferably, (ii) treated with chromium-(II)-acetate in the presence of an organic base and (IV) reacted without isolation with NaBH 4  to give (V), this is oxidized to a corresponding 20 - hydroxy - 16 - oxo - 18 - acid lactone (18 # 20), this is converted to a 15-halo derivative and this dehydrohalogenated to give (VI), this is reduced with a lithium-aluminium trialkoxyhydride to give (VII), this is epoxidized with a peracid to give (VIII), this is reduced to give (IX) and this is either (i) treated with acetone in the presence of an acidic catalyst to give (X), this converted to a 16#-(C 1-5  acylate). this hydrolysed to a 3 - OY 11 - Z - 14#, 18,20- trihydroxy - 16# - (C 1-5  acyloxy) - steroid, this hydrolysed to (XI), this heated with ammonia or an alkylamine in an inert solvent to give XII, and this reduced to give (XIII) which is N- acylated to give (XIV) by reaction with X-CH 2 -CO 2 H (X is a halogen atom or a free or esterified hydroxyl group) or a halide or an hydride thereof, or (ii) reacted with a triaryl halomethane to give (IXa), this partially acylated to give (IXb), this hydrolysed in an acidic medium to give (IXc), this oxidized to give (IXd), this reacted with ammonia or an alkylamine in an inert solvent and reduced to give (IXe) and this N-acylated as described above. In the products acylated hydroxy groups may be hydrolysed and free hydroxy groups acylated. 3α,11α - Diacetoxy - 16α,17 - epoxy - 5#- pregnan - 20 - one is prepared by microbiologically hydroxylating 16α,17-epoxy-pregn-4-one- 3,20 - dione to give 11α - hydroxy - 16α,17 - epoxypregn-4-ene-3,20-dione, converting this to the 11- acetate, hydrogenating this to 11α-acetoxy-16α- 17 - epoxy - 5# - pregnane 3,20 - dione, reducing this to 3α - hydroxy - 11α- acetoxy - 16α,17- epoxy - 5#- pregnan - 20 - one and acetylating this. The novel 18-acylamino steroids (XIV) are stated to lower blood pressure and act as diuretics, and they may be made up into pharmaceutical compositions with suitable carriers.